tbuckley/cabot-search huggingface dataset:
A Systematic Review of Mercury Exposures from Skin-Lightening Products
Authors: Ashley Bastiansz, Jessica Ewald, Verónica Rodríguez Saldaña, Andrea Santa-Rios, Niladri Basu
Journal: Environmental Health Perspectives (2022)

Background: The Minamata Convention on Mercury (Article 4) prohibits the manufacture, import, or export of skin-lightening products containing mercury concentrations above 1 ppm. However, there is a lack of knowledge surrounding the global prevalence of mercury-added skin-lightening products. Objective: The objective of this study was to increase our understanding of worldwide human mercury exposure from skin-lightening products. Methods: A systematic search of peer-reviewed scientific literature was performed for relevant articles in four databases (PubMed, Web of Science Core Collection, Scopus, and TOXLINE). The search strategy, eligibility criteria, and data-extraction methods were established a priori. The search identified 2,303 unique scientific articles, of which 41 were ultimately deemed eligible for inclusion after iterative screens at the title, abstract, and whole-text levels. To facilitate data extraction and synthesis, all papers were organized according to four data groups a) "Mercury in products," b) "Usage of products," c) "Human biomarkers of exposure," and d) "Health impacts." Results: This review was based on data contained in 41 peer-reviewed scientific papers from 22 countries worldwide published between 2000 and 2022. In total, we captured mercury concentration values from 787 skin-lightening product samples [overall pooled central median mercury level was 0.49μg/g; interquartile range (IQR): 0.02–5.9] and 1,042 human biomarker measurements from 863 individuals. We also synthesized usage information from 3,898 individuals and self-reported health impacts associated with using mercury-added products from 832 individuals. Discussion: This review suggests that mercury widely exists as an active ingredient in many skin-lightening products worldwide and that users are at risk of variable and often high exposures. These synthesized findings identify data gaps and help increase our understanding of the health risks associated with the use of these products. https://doi.org/10.1289/EHP10808
Maternal hypertensive disorder of pregnancy and mortality in offspring from birth to young adulthood: national population based cohort study
Journal: BMJ (2022)

pregnancy education the follow-up times and rates should be, respectively: 410 007.82 and 47.56 for HDP and high education, 19 663 051.26 and 36.62 for no HDP and medium education, and 14 270 138.85 and 57.25 for no HDP and low education.
Local IL-23 is required for proliferation and retention of skin-resident memory T <sub>H</sub> 17 cells
Authors: Sarah K. Whitley, Mushi Li, Sakeen W. Kashem, Toshiro Hirai, Botond Z. Igyártó, Kelley Knizner, Jonhan Ho, Laura K. Ferris, Casey T. Weaver, Daniel J. Cua, Mandy J. McGeachy, Daniel H. Kaplan
Journal: Science Immunology (2022)

The cytokine interleukin-23 (IL-23) is critical for development and maintenance of autoimmune inflammation in nonlymphoid tissues; however, the mechanism through which IL-23 supports tissue-specific immunity remains unclear. In mice, we found that circulating memory T cells were dispensable for anamnestic protection from Candida albicans skin infection, and tissue-resident memory (TRM) cell-mediated protection from C. albicans reinfection required IL-23. Administration of anti-IL-23 receptor antibody to mice after resolution of primary C. albicans infection resulted in loss of CD69+ CD103+ tissue-resident memory T helper 17 (TRM17) cells from skin, and clinical anti-IL-23 therapy depleted TRM17 cells from skin of patients with psoriasis. IL-23 receptor blockade impaired TRM17 cell proliferation but did not affect apoptosis susceptibility or tissue egress. IL-23 produced by CD301b+ myeloid cells was required for TRM17 maintenance in skin after C. albicans infection, and CD301b+ cells were necessary for TRM17 expansion during the development of imiquimod dermatitis. This study demonstrates that locally produced IL-23 promotes in situ proliferation of cutaneous TRM17 cells to support their longevity and function and provides mechanistic insight into the durable efficacy of IL-23 blockade in the treatment of psoriasis.
We must value and safeguard human health for a sustainable future
Authors: Neena Modi, Sonia Bhalotra, Flavia Bustreo, Mark Hanson
Journal: BMJ (2022)

Do policy makers value human health?Although the immediate answer may be "yes," reflection suggests a more nuanced response.During the covid-19 pandemic many policy makers have presented the preservation of health and economic growth as opposing choices.And there have been troubling displays of vaccine nationalism from leaders seemingly unable to comprehend that no one is safe until everyone is protected.Meanwhile, cultures and religions around the world, supported by legislation, continue to obstruct efforts to improve reproductive health by barring access to contraception and abortion.Earlier this year the United States, in an extraordinary reversal of societal progress, overturned the landmark Roe v Wade ruling and severely restricted access to safe abortion.
More people survived a cardiac arrest when first aiders received an app alert
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Chris Smith
Journal: BMJ (2022)

The studySmith CM, Lall R, Fothergill RT, Spaight R, Perkins GD. The effect of the GoodSAM volunteer first-responder app on survival to hospital discharge following out-of-hospital cardiac arrest. Eur Heart J Acute Cardiovasc Care 2022;11:20-31.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/more-people-survived-cardiac-arrest-first-aiders-goodsam-alert/.
Retraction Note to: LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis
Authors: Fengting Huang, Wenying Chen, Juanfei Peng, Yuanhua Li, Yanyan Zhuang, Zhe Zhu, Chunkui Shao, Wanling Yang, Herui Yao, Shineng Zhang
Journal: Molecular Cancer (2022)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-018-0845-6.
When I use a word . . . . Too much healthcare—observational studies
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

Observational studies generally provide less reliable evidence than well designed randomised trials and systematic reviews and meta-analyses of such trials. Their results can be affected by confounders, colliders, and a wide range of biases, and they are likely to overestimate effect sizes in studies of benefits. However, they do have their uses and are likely to give different types of information. Systematic reviews and meta-analyses of observational studies are generally discouraged, except in some cases, including studies of children, pregnant women, and older people, and in other cases when randomised trials are not possible or to inform the design of such trials. In studies of adverse drug reactions, observational studies may suggest associations when none exists. Over-reliance on observational studies of poor quality during covid-19 has led to misleading results.
High salt intake activates the hypothalamic–pituitary–adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
Authors: Hannah M Costello, Georgios Krilis, Celine Grenier, David Severs, Alicja Czopek, Jessica R Ivy, Mark Nixon, Megan C Holmes, Dawn E W Livingstone, Ewout J Hoorn, Neeraj Dhaun, Matthew A Bailey
Journal: Cardiovascular Research (2022)

Abstract Aims High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the hypothalamic–pituitary–adrenal axis activation and leads to sustained glucocorticoid excess. Methods and results In male C57BL/6 mice, high salt intake for 2–8 weeks caused an increase in diurnal peak levels of plasma corticosterone. After 2 weeks, high salt increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, consistent with basal hypothalamic–pituitary–adrenal axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced axis sensitivity. The binding capacity of Corticosteroid-Binding Globulin was reduced and its encoding mRNA downregulated in the liver. In the hippocampus and anterior pituitary, Fkbp5 mRNA levels were increased, indicating increased glucocorticoid exposure. The mRNA expression of the glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase Type 1, was increased in these brain areas and in the liver. Sustained high salt intake activated a water conservation response by the kidney, increasing plasma levels of the vasopressin surrogate, copeptin. Increased mRNA abundance of Tonebp and Avpr1b in the anterior pituitary suggested that vasopressin signalling contributes to hypothalamic–pituitary–adrenal axis activation by high salt diet. Conclusion Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells.
Isoform changes of action potential regulators in the ventricles of arrhythmogenic phospholamban-R14del humanized mouse hearts
Authors: Malgorzata E Rogalska, Elizabeth Vafiadaki, Zoi Erpapazoglou, Kobra Haghighi, Lisa Green, Christos S Mantzoros, Roger J Hajjar, Michael Tranter, Ioannis Karakikes, Evangelia G Kranias, Francesca Stillitano, Panagiota Kafasla, Despina Sanoudou
Journal: Metabolism (2022)
On demand regulation of blood glucose level by biocompatible oxidized starch-Con A nanogels for glucose-responsive release of exenatide
Authors: Jie Bai, Huijuan Zhang, Zhi Yang, Pinglan Li, Bin Liu, Dan Li, Shuang Liang, Qimeng Wang, Zekun Li, Jipeng Zhang, Shanan Chen, Guohua Hou, Yuan Li
Journal: Journal of Controlled Release (2022)
Lipid-polymer hybrid nanoparticle with cell-distinct drug release for treatment of stemness-derived resistant tumor
Authors: Shiyang Shen, Teng Li, Jinyi Fan, Quanlin Shao, He Dong, Xiao Xu, Ran Mo
Journal: Acta Pharmaceutica Sinica B (2022)

Drug resistance presents one of the major causes for the failure of cancer chemotherapy. Cancer stem-like cells (CSCs), a population of self-renewal cells with high tumorigenicity and innate chemoresistance, can survive conventional chemotherapy and generate increased resistance. Here, we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent, all-trans retinoic acid and the chemotherapeutic drug, doxorubicin to overcome the CSC-associated chemoresistance. The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation. In the hypoxic CSCs, ATRA is released to induce differentiation of the CSCs, and in the differentiating CSCs with decreased chemoresistance, DOX is released upon elevation of reactive oxygen species to cause subsequent cell death. In the bulk tumor cells, the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect. This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism. We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.
An injectable bioactive dressing based on platelet-rich plasma and nanoclay: Sustained release of deferoxamine to accelerate chronic wound healing
Authors: Jiao Zhang, Qian Luo, Qian Hu, Tiantian Zhang, Jingyu Shi, Li Kong, Dehao Fu, Conglian Yang, Zhiping Zhang
Journal: Acta Pharmaceutica Sinica B (2022)

Delayed diabetic wound healing has placed an enormous burden on society. The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis. Platelet-rich plasma (PRP) gel, a popular biomaterial in the field of regeneration, has limited applications due to its non-injectable properties and rapid release and degradation of growth factors. Here, we prepared an injectable hydrogel (DPLG) based on PRP and laponite by a simple one-step mixing method. Taking advantages of the non-covalent interactions, DPLG could overcome the limitations of PRP gels, which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine (an angiogenesis promoter). DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in type I diabetic rats and normal rats. Taken together, this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.
Sustained release of hydrogen sulfide from anisotropic ferrofluid hydrogel for the repair of spinal cord injury
Authors: Ruofei Wang, Xia-Xiao Wu, Zhenming Tian, Tian Hu, Chaoyang Cai, Guan-Ping Wu, Gang-Biao Jiang, Bin Liu
Journal: Bioactive Materials (2022)

Spinal cord injury (SCI) results in massive neuronal death, axonal disruption, and cascading inflammatory response, which causes further damage to impaired neurons. The survived neurons with damaged function fail to form effective neuronal circuits. It is mainly caused by the neuroinflammatory microenvironment at injury sites and regenerated axons without guidance. To address this challenge, a ferrofluid hydrogel (FFH) was prepared with Ferric tetrasulfide (Fe3S4), carboxymethyl chitosan, and gold. Its internal structural particles can be oriented in a magnetic field to acquire anisotropy. Moreover, Fe3S4 can release hydrogen sulfide (H2S) with anti-inflammatory effects under acidic conditions. Regarding in vitro experiments, 0.01g/ml Fe3S4 FFH significantly reduced the inflammatory factors produced by LPS-induced BV2 cells. Oriented and longer axons of the induced neural stem cells loaded on anisotropic FFH were observed. In vivo experiments showed that FFH reduced the activated microglia/macrophage and the expression of pro-inflammatory factors in SCI rats through the NF-κB pathway. Moreover, it significantly promoted directional axonal regrowth and functional recovery after SCI. Given the critical role of inhibition of neuroinflammation and directional axonal growth, anisotropic Fe3S4 FFH is a promising alternative for the treatment of SCI.
ALT Is Not Associated With Achieving Subcirrhotic Liver Stiffness and HCC During Entecavir Therapy in HBV-Related Cirrhosis
Authors: Mi Na Kim, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Se Young Jang, Won Young Tak, Young-Oh Kweon, Soo Young Park, Seung Up Kim
Journal: Clinical Gastroenterology and Hepatology (2022)
MF-SuP-pKa: Multi-fidelity modeling with subgraph pooling mechanism for pKa prediction
Authors: Jialu Wu, Yue Wan, Zhenxing Wu, Shengyu Zhang, Dongsheng Cao, Chang-Yu Hsieh, Tingjun Hou
Journal: Acta Pharmaceutica Sinica B (2022)

Acid-base dissociation constant (pKa) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pKa prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pKa (multi-fidelity modeling with subgraph pooling for pKa prediction), a novel pKa prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledge-aware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pKa prediction. To overcome the scarcity of accurate pKa data, low-fidelity data (computational pKa) was used to fit the high-fidelity data (experimental pKa) through transfer learning. The final MF-SuP-pKa model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pKa achieves superior performances to the state-of-the-art pKa prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pKa achieves 23.83% and 20.12% improvement in terms of mean absolute error (MAE) on the acidic and basic sets, respectively.
Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition
Authors: Yaochen Xie, Qian Zhou, Qiaojun He, Xiaoyi Wang, Jincheng Wang
Journal: Acta Pharmaceutica Sinica B (2022)

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.
Antibacterial gas therapy: Strategies, advances, and prospects
Authors: Tian-Yu Wang, Xiao-Yu Zhu, Fu-Gen Wu
Journal: Bioactive Materials (2022)

One of the challenges posed by current antibacterial therapy is that the expanded and massive use of antibiotics endows bacteria with the ability to resist almost all kinds of antibiotics. Therefore, developing alternative strategies for efficient antibacterial treatment is urgently needed. Antibacterial gas therapy has attracted much attention in the past decade. Nitric oxide (NO), carbon monoxide (CO), sulfur dioxide (SO2), hydrogen sulfide (H2S), and hydrogen (H2) are not only known as endogenous signaling molecules, but also play critical roles in many pathological processes. These gases are considered as attractive bactericidal agents because they are able to kill bacteria, disperse biofilms, and promote bacteria-infected wound healing while avoiding resistance. In this review, we discuss the bactericidal properties of these gases, as well as the recent advances of gas-involving systems in antibacterial, antibiofilm, and wound treatment applications. Moreover, we summarize various gas donors utilized in antibacterial treatment. We hope this review will shed new light on the future design and applications of advanced antibacterial gas therapy.
Small molecule-based immunomodulators for cancer therapy
Authors: Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen
Journal: Acta Pharmaceutica Sinica B (2022)

Immunotherapy has led to a paradigm shift in the treatment of cancer. Current cancer immunotherapies are mostly antibody-based, thus possessing advantages in regard to pharmacodynamics (e.g., specificity and efficacy). However, they have limitations in terms of pharmacokinetics including long half-lives, poor tissue/tumor penetration, and little/no oral bioavailability. In addition, therapeutic antibodies are immunogenic, thus may cause unwanted adverse effects. Therefore, researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy, as small molecules may overcome the above disadvantages associated with antibodies. Further, small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment, and may be combined to elicit synergistic effects. Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy. In this review, we describe the current progress in small molecule-based immunomodulators (inhibitors/agonists/degraders) for cancer therapy, including those targeting PD-1/PD-L1, chemokine receptors, stimulator of interferon genes (STING), Toll-like receptor (TLR), etc. The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.
Bone/cartilage targeted hydrogel: Strategies and applications
Authors: Hao Zhang, Shunli Wu, Weikai Chen, Yan Hu, Zhen Geng, Jiacan Su
Journal: Bioactive Materials (2022)

The skeletal system is responsible for weight-bearing, organ protection, and movement. Bone diseases caused by trauma, infection, and aging can seriously affect a patient's quality of life. Bone targeted biomaterials are suitable for the treatment of bone diseases. Biomaterials with bone-targeted properties can improve drug utilization and reduce side effects. A large number of bone-targeted micro-nano materials have been developed. However, only a few studies addressed bone-targeted hydrogel. The large size of hydrogel makes it difficult to achieve systematic targeting. However, local targeted hydrogel still has significant prospects. Molecules in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted hydrogel. Drug delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted hydrogel. Besides, injectable hydrogel drug depot carrying bone-targeted drugs is another strategy. In this review, we summarize the bone-targeted hydrogel through application environment, construction strategies and disease applications. We hope this article will provide a reference for the development of bone-targeted hydrogels. We also hope this article could increase awareness of bone-targeted materials.